The 2011–12 C.D. Motagua season in the Honduran Liga Nacional was C.D. Motagua's 61st season in its history; the domestic league was divided into two tournaments, Apertura and Clausura. The Apertura started on 7 August, but due to its participation in the 2011–12 CONCACAF Champions League, their first official game was played on 28 July 2011. Motagua, as title holders, were looking for its 13th domestic championship, and its first CONCACAF achievement. The pre-season started on 20 June 2011.

The club announced its first signing on 29 April 2011, Honduran striker Luis López arrived for a one-year contract. Also, 37-year-old goalkeeper Kerpo de León joined after a prominent performance at C.D.S. Vida. On 3 June, Honduran midfielder Carlos Discua was transferred from Guatemalan side C.S.D. Comunicaciones. In the evening of 15 June 2011, midfielder Jorge Claros was shot twice in the head and clavicle by two unidentified persons who tried to steal his car in a neighbor in San Pedro Sula, Claros escaped injured but in a stable condition. On 22 August, the club signed 22-year-old Colombian striker John Palacios from ASA.

Motagua's first game in the league was on 7 August at Estadio Fausto Flores Lagos against C.D. Necaxa losing 0–1. On 16 August, due to poor performance both in the league and the Champions League, the club's president Pedro Atala took the decision to separate Ramón Maradiaga as manager; leaving Luis Reyes as a temporary replacement. Three days later, on 19 September, Mexican coach José Treviño arrived as new manager for the rest of the season; while Colombian striker John Palacios left the team just one month after his signing arguing differences with teammates.

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