Mukesh made his debut in the film Baloon (1982). He gained prominence for both his comedy and drama centered roles, in films such as Odaruthammava Aalariyam (1984), Boeing Boeing (1985), Shyama (1986), Adiverukal (1986), Thaniyavarthanam (1987), Sangam (1988) and Vandanam (1989). Mukesh’s role as Gopalakrishnan in Ramji Rav Speaking (1989) saw a rebirth in his career, a new type of stock character emerged based on Mukesh’s stardom. A youthful, funny, and fraudulent young man who had to go against the law due to life’s pressures and circumstances. This period saw the shift of Mukesh as a bankable lead actor, especially due to the box-office success of In Harihar Nagar (1990) and Godfather (1991). This led to a series of low-budget comedy films such as Innathe Programme (1991), Ennodishtam Koodamo (1992), Poochakkaru Mani Kettum (1994), Malappuram Haji Mahanaya Joji (1994), and Sipayi Lahala (1995).
By the late 1990s, Mukesh continued his roles in comedy B movies. With films such as Mr. Clean (1996), Oru Mutham Mani Mutham (1997), Kalyana Kacheri (1997), Mattupetti Machan (1998), and Aakasha Ganga (1999). His more prominent roles would be in Siddique’s Hitler (1996) and Friends (1999). He had a re-union with Priyadarshan with Kakkakuyil (2001). Post 2000, Mukesh went into another shift of his career. He started doing more character roles. Some of them being Chronic Bachelor (2003), Sethurama Iyer CBI (2004), Udayananu Tharam (2005), Rasathanthram (2006), and Vinodayathra (2007). His performance as Nara Pilla in Adoor Gopalakrishnan’s Naalu Pennungal (2007) was noticed as well.
In 2007, Mukesh turned to production as well. He formed Lumiere Film Company along with Sreenivasan. Their first venture was Katha Parayumpol (2007).