Mikulak was born in Corona del Mar, California, and attended Corona del Mar High School. His parents both competed in gymnastics at the University of California, Berkeley, and started Sam in gymnastics at age two. His father, Stephen Mikulak, is an orthopedic surgeon. Mikulak was a member of the Junior National team from 2007 to 2010. He won the all-around championship as well as event championships in the floor exercise and vault at the 2010 Junior Olympic Nationals.
Mikulak enrolled at the University of Michigan where he was a member of the Michigan Wolverines men's gymnastics team. As a freshman in 2010–2011, he won the individual all-around title at the 2011 NCAA Men's Gymnastics championship with a career-high score of 90.75. As a sophomore in 2012, he won the Big Ten Conference championship in the high bar with a 15.45 score and pommel horse with a 15.55 score. He finished third in the all-around competition at the 2012 NCAA championship. Mikulak was the first American member of the University of Michigan men's artistic gymnastics team to qualify for the Olympic games. Mikulak won the all-around, parallel bars and high bar competitions at the 2013 NCAA championship. He won the all-around and parallel bars competitions at the 2014 NCAA championship. Mikulak was an anchor on the University of Michigan men's team which captured the NCAA team championship in 2013 and 2014. He was named undergraduate assistant coach for the University of Michigan men's team in August 2014.
On July 1, 2012, he was selected for the five-man US men's gymnastics team and represented the country at the 2012 Summer Olympics in London. He was the first male gymnast from the University of Michigan to be named to the U.S. Olympic team. He was chosen for the Olympic team despite being unable to compete in five of the six events after spraining his ankle while competing on the vault on the first night of Olympic trials.
The US team came in 5th place during the team final. Mikulak competed in the vault final, placing 5th. His Michigan teammate Syque Caesar also competed in the 2012 Olympics, representing Bangladesh.
Mikulak participated in the 2013 World Artistic Gymnastics Championships. He placed 6th in the all-around final and 4th in the high bar final. He participated in the P&G U.S. Championships in Hartford and placed first in all-around, parallel bars and high bar final.
Mikulak participated in the 2014 P&G U.S. Championships in Pittsburgh. He placed first overall in all-around final and pommel horse and second in high bar. He participated in the World Championships in 2014 in Nanning, China, representing Team USA. He won a bronze medal with the US team in the team competition and finished 12th in the men's individual championships.
Mikulak, with Simone Biles, MyKayla Skinner and Donnell Whittenburg, represented the U.S. against a strong international field at the 2015 AT&T American Cup, on March 7 at AT&T Stadium in Arlington, Texas. Mikulak finished fourth in the individual all-around competition.
On July 11, 2015, Mikulak led the U.S. men's gymnastics team to their first gold medal at the Pan-American Games in twenty years. Two days later, he was crowned Pan American champion in the all-around final.
On August 16, 2015, Mikulak won his third consecutive all-around title at the P&G Championships held in Indianapolis. His score was 183.650. Mikulak earned five medals. He won vault and parallel bars and took third on pommel horse and high bar. Due to an injury, he was unable to participate in the 2015 World Artistic Gymnastics Championships held in Glasgow, Scotland.
On December 17, 2015 Mikulak and two-time World medalist Donnell Whittenburg accepted invitations to represent the United States at the 2016 AT&T American Cup at Prudential Center in Newark, N.J., on March 5, 2016.
On February 21, 2016 Mikulak won the all-around title at the Winter Cup Challenge at Las Vegas' Cashman Center, with a two-day score of 177.50. He bested Akash Modi of Stanford University who finished in second place with a score of 175.300 and Sean Melton of Ohio State University who finished in third place with a score of 174.500. Mikulak finished fourth at the American Cup in March in New Jersey, in his first international competition since recovering from a torn Achilles. Three-time national champion Mikulak and fellow 2012 Olympic teammates John Orozco and Jake Dalton headlined the U.S. men's team at the 2016 Pacific Rim Championships in Everett, Washington, April 8–10, 2016.
Mikulak claimed his fourth consecutive men's crown June 5, 2016 at the P&G Gymnastics Championships in Hartford, Connecticut. He outpointed Chris Brooks 181.500 to 179.850 to become the first competitor to win four-in-a-row since Blaine Wilson collected five between 1996 and 2000.
On June 25, 2016, Mikulak was once again named to the five-man United States men's gymnastics team for the Olympics. He represented the United States at the 2016 Summer Olympics in Rio de Janeiro alongside Jake Dalton, Danell Leyva, Alex Naddour, and Chris Brooks. Mikulak posted the highest all-around score at the U.S. Olympic trials in St. Louis. Mikulak finished in seventh position in the men's all-around finals competition at the Rio Summer Olympic Games. His USA men's gymnastics team of five finished fifth overall in the team competition (after sitting second in the first round of Rio competition). Mikulak's best performance individually in Rio was a fourth-place finish in the High Bar competition.
He trains at the U.S. Olympic Training Center in Colorado Springs, Colorado.
Mikulak maintained his spot on the United States National Team at the 2017 P&G Championships held August 17-19. Mikulak, who had his streak of four U.S. national all-around titles snapped due to injury, competed on only two events while recovering from an Achilles tendon injury that he suffered at the Winter Cup. The veteran rose to the occasion on those two events, as he took second on pommel horse (29.600) and third on high bar (27.850). He will be a part of the six-man group that will represent the United States at the 2017 FIG World Championships October 2-8, 2017 in Montreal.