Born in Bailén, Jaén, Andalusia, Manzano's training career started in 1983 at the age of 27. He took charge of several teams in his native region, including Real Jaén in the fourth division.
In 1996, Manzano signed with Talavera CF from the third level. During his two-season spell he led the Castile-La Mancha club to a second-place finish in its group (1996–97), and a narrow miss on promotion (1997–98). His good work there prompted the interest – and signing – from division two's CD Toledo, which he helped retain their league status with a comfortable seventh place.
Manzano had his first La Liga experience with Real Valladolid, in 1999–2000. His new club finished eighth, and the season included a 1–0 win over Real Madrid at the Santiago Bernabéu Stadium. For the following campaign, he stayed in the top flight with Racing de Santander; in spite of a 4–0 home success against FC Barcelona, the Cantabrians were relegated and the coach was fired.
After helping Rayo Vallecano finish 11th in 2001–02's top division, Manzano signed for RCD Mallorca. Season highlights were another win at Real Madrid (5–1) and the conquest of the Copa del Rey, over Recreativo de Huelva.
Subsequently, Manzano signed with Atlético Madrid, nearly qualifying the side for the UEFA Cup after finishing seventh. After the sacking of Iñaki Sáez as Spain national team coach, he was rumoured to be one of his possible successors, but nothing came of it, and he took charge of Málaga CF instead.
On 15 February 2006, Manzano returned to Mallorca after Héctor Cúper's dismissal, and continued to work with the Balearic Islands club in the following seasons. In 2009–10 the team won their first ten home fixtures, eventually only losing three of the 19 in the league (Sevilla FC, Barcelona and Real Madrid) and qualifying for the Europa League, as fifth.
On 19 May 2010, it was announced Mallorca would not renew Manzano's contract despite his achievements, due to financial difficulties. On 26 September he returned to active, being appointed at Sevilla as a replacement for fired Antonio Álvarez.
On 8 June 2011, after leading Sevilla to the fifth place, with the subsequent Europa League qualification, Manzano returned to former team Atlético Madrid after replacing Quique Sánchez Flores. Early into 2011–12, he and José Antonio Reyes had a serious altercation which resulted in the player being relegated to the bench and sometimes not even selected for matchday squads.
On 22 December 2011, following a 0–1 home and 1–3 aggregate loss against Albacete Balompié for the domestic cup, Manzano was relieved of his duties, as the club also ranked 10th in the domestic league. On 5 February 2013, he returned to Mallorca for a third spell following the sacking of Joaquín Caparrós, as the campaign went on to end in top level relegation.
On 11 February 2014, Manzano was appointed at Beijing Guoan F.C. in the Chinese Super League. He continued working in that competition in the following years.As of 30 October 2016
Copa del Rey: 2002–03
Don Balón Award – Coach of the Year: 2008
Chinese Football Association Coach of the Year: 2014