He experimented with voice recordings during his employment in Delhi and gradually developed his singing abilities and also his musical instrumental skills.

His first hit song as a playback singer was "Dil Jalta Hai To Jalne De" for actor Motilal in 1945 with the film Pehli Nazar with music composed by Anil Biswas and lyrics written by Aah Sitapuri.

Initially Mukesh was the ghost voice of Dilip Kumar in this movie and Mohammed Rafi sang for Raj Kapoor.

Other composers who used Mukesh voice for great Dilip Kumar in hit songs like "Jeevan Sapna toot gaya" were Anil Biswas in Anokha Pyar, Ye Mera Diwanapan hai, Shankar–Jaikishan in Yahudi and Suhana Safar and Dil Tadap Tadap ke, Salil Choudhary in Madhumati.

From "Naina hai jadoo bhare..." Bedard Zamana Kya Jane (1958) composed by Kalyanji alone as Kalyanji Virji Shah, and "Main hoon mast madari..." Madari (1959) as the first Kalyanji-Anandji-Mukesh combo, to "Chahe aaj mujhe napasand karo" Darinda 1977, the K-A, Mukesh combination gave numerous popular songs like "Chhalia mera naam...", "Mere toote hue dil se...", "Dum dum diga diga" Chalia (1959), "Mujhko iss raat ki tanhai mein..." Dil Bhi Tera Hum Bhi Tere (1960), "Hum chhod chale hain mehfil ko..." (Ji Chahta Hai), "Humne tumko pyar kiya hai jitna..." (Dulha Dulhan), "Chal mere dil lehraake chal..." Ishara and "Dheere se chalo..." Johar Mehmood in Goa, "Main to ek khwab hoon..." and "Chand si mehbooba ho..." Himalay Ki Godmein(1965), "Waqt kartaa jo wafaa..." Dil Ne Pukara, "Deewanon se yeh mat poocho..." Upkar, "Khush raho har khushi hai..." Suhaag Raat and "Humsafar ab yeh safar kat jaayega..." Juari, "Chandi ki deewaar..." and "Le chal le chal mere jeevan saathi..." Vishwas (1969), "Koi jab tumhara hriday tod de..." Purab Aur Paschim, "Darpan ko dekha..." Upaasna, "Jo tumko ho pasand..." Safar and "Mujhe nahin poochni tumse beeti baatein..." Anjaan Raahein (1970).

Out of the numerous songs he gave his voice to, "Kahin door jab din dhal Jaaye" from Anand (1971),[11] "Ek Pyaar ka Nagma hai" from Shor (1972), "Maine Tere Liye Hi Saat Rang Ke" from Anand (1971), "Sab Kuch Seekha Humne" from Anari (1959), "Jeena yahan marna yahan" and "Kehta hai Joker" from Mera Naam Joker (1971) are the most popular among his fans and followers.

[citation needed] Mukesh started his career as an actor singer in the film Nirdosh in 1941, with Nalini Jaywant as his heroine.

They got married in a temple in Kandivali on 22 July 1946, Mukesh's 23rd birthday, with the help of the actor Motilal and from the residence of R. D. Mathur.

[24][citation needed] His body was flown to India by Mangeshkar, where a grand funeral ceremony was held in the presence of several actors, with personalities of the Indian film industry and fans paying tribute.

After Mukesh's death, his newer, hitherto unreleased, songs were released in 1977 in films such as Dharam Veer, Amar Akbar Anthony, Khel khiladi ka, Darinda and Chandi sona.

The year 1978 also featured a considerable number of Mukesh's songs in films such as Aahuti, Paramatma, Tumhari kasam and Satyam Shivam Sundaram, where Mukesh sang his last film song Chanchal sheetal nirmal komal for Raj Kapoor's younger brother, Shashi Kapoor.

From 1980 onward, Mukesh's voice was heard in many later released films such as Shaitan mujarim, Premika, Patthar se Takkar (1980), Sanjh ki Bela, Maila Anchal (1981), Aarohi (1982), Chor Mandali (1983), Nirlaj (1985), Love and God (1986), Shubh Chintak (1989), and his last known release of Chand Grahan (1997).