When Omameh was in sixth grade, he did not know what American football was and when he asked his father about it, his father brought out a soccer ball. On the first day of football practice, he wore sandals and a wristwatch. As a senior at St. Francis DeSales High School in Columbus, Ohio, Omameh was selected as a 2007 Division II All-Ohio first team offensive lineman and member of The Columbus Dispatch All-metro team. He was a straight-A student recruited by the likes of Princeton University and Massachusetts Institute of Technology. Omameh matriculated at Michigan as the lowest rated prospect in the 24-man entering class of 2008 according to Rivals.com. He also earned three varsity letters in track & field and one in basketball.
Omameh redshirted as a freshman for the 2008 Michigan Wolverines. He made his first career start on November 7, 2009 when Perry Dorrestein was sidelined with a back injury against Purdue, and Omameh stayed in the starting lineup for the final two games of the season for the 2009 team. Despite being Michigan's lowest rated prospect in the entering class of 2008, he went on to start for the team for three and a half seasons. By the end of the 2012 Michigan–Ohio State game, Omameh had started 41 consecutive games.
Omameh has been known for eating prowess since high school, once eating 30 White Castle hamburgers. Even other offensive linemen, such as teammate Taylor Lewan, marveled at his appetite. This helped Omameh bulk up from about 240 pounds (110 kg) as a freshman to over 300 pounds (140 kg) two years later when he became a regular starting offensive lineman.
At Michigan, he had difficulty understanding quarterback Denard Robinson's playcalling in the huddle because of Robinson's rapid speech pattern. In 2010, Omameh was a nominee to be the University of Michigan homecoming king. Omameh was an Academic All-Big Ten in both 2010 and 2011.
On September 18, 2012, Omameh was named to the 11-man Allstate American Football Coaches Association (AFCA) Good Works Team. His Good Works team recognition was for his weekly appearances at the C.S. Mott Children's Hospital. He joins Zoltan Mesko as the only two Michigan players to ever receive the AFCA Good Works Team recognition. On November 13, Omameh was named a finalist for the 2012 Pop Warner National College Football Award. Omameh was a first team All-Big Ten selection by the coaches and an honorable mention selection by the media. He earned his third consecutive Academic All-Big Ten recognition in 2012.
Omameh signed an undrafted free agent contract with the San Francisco 49ers following the 2013 NFL Draft. Omameh was cut during the final preseason roster moves on August 31, 2013 and signed to the practice squad two days later.
On October 11, 2013, the Tampa Bay Buccaneers signed Omameh off of the 49ers' practice squad. He started all 16 games for the Buccaneers at the right guard position during the 2014 season. The Buccaneers cut Omameh before the 2015 season on September 5, 2015.
On September 6, 2015, Omameh was signed the following day to the Chicago Bears after he cleared waivers. After playing 679 snaps for the Bears, he became an unrestricted free agent, but was expected to return to the team.
Omameh signed with the Jacksonville Jaguars on June 2, 2016. He was placed on injured reserve on November 21, 2016 after sustaining a left foot injury in Week 11 against the Detroit Lions.
On March 7, 2017, Omameh re-signed with the Jaguars.
Omameh's parents, Phyllis and Patrick Sr., moved to Columbus, Ohio from Nigeria in the early 1980s. His father is 5 foot 10 inches (1.78 m) and his mother is 5 foot 6 inches (1.68 m).