Cutugno began his musical career as a drummer, and at 19 he founded his first band, Toto e i Tati. He later formed the disco band Albatros together with Lino Losito and Mario Limongelli. He also started a career as a songwriter, contributing some of French-American singer Joe Dassin most well-known songs such as “L’été indien“, “Et si tu n’existais pas“, and “Le Jardin du Luxembourg” (written with Vito Pallavicini). He also co-wrote Dalida’s “Monday Tuesday… Laissez moi danser” (“Voglio l’anima” in its Italian version), which achieved Platinum record status shortly after being released, as well as songs for Johnny Hallyday, Mireille Mathieu, Ornella Vanoni, Domenico Modugno, Claude François, Gigliola Cinquetti, Gérard Lenorman, Michel Sardou, Hervé Vilard, and Paul Mauriat.

In 1976, Albatros participated for the first time in the Sanremo Music Festival finishing in third place with the song “Volo AZ 504“. Following another chart success with the song “Santamaria de Portugal“, in 1978 Cutugno left Albatros to concentrate on his solo career. The same year he had his first solo hit with “Donna donna mia“, the opening song of the Mike Bongiorno’s RAI TV show Scommettiamo?. In 1979, he wrote Adriano Celentano’s number one hit “Soli“.

In 1980, Cutugno returned to the Sanremo Music Festival and won the competition with the song “Solo noi” (“Only us”). However, Cutugno’s affiliation with the festival is mostly remembered for “L’Italiano” (“The Italian”), a song he presented in 1983. Originally intended for Adriano Celentano – who declined to sing it because, despite liking the song, he did not feel comfortable singing the refrain sono un italiano vero (“I am a true Italian“) – “L’Italiano“‘s recapitulation of some of Italy’s most popular social traits made the song very popular with Italian expats. Although the song finished only fifth in Sanremo, it went on to become Cutugno’s biggest international hit. Cutugno would finish second in six more editions of the Sanremo festival: in 1984 with the song “Serenata” (“Serenade”); in 1987 with “Figli” (“Children”); in 1988 with “Emozioni” (“Emotions”); in 1989 with the song “Le mamme” (“Mothers”); in 1990 with the song “Gli amori” (“Loves”, but entitled “Good Love Gone Bad” in Ray Charles’s version); and in 2005 with Annalisa Minetti with the song “Come noi nessuno al mondo” (“No one else in the world like us”); a record which would lead him to be nicknamed “the eternal second” (l’eterno secondo). Cutugno shares the record for the highest number of participations in the festival – 15, namely in 1976, 1977, 1980, 1983, 1984, 1986, 1987, 1988, 1989, 1990, 1995, 1997, 2005, 2008, and 2010; one of only five artists (as of 2023), the others being Al Bano, Anna Oxa, Milva and Peppino di Capri. In 2013, Cutugno was awarded a lifetime career award at the Sanremo Festival.

As a songwriter, during the 1980’s Cutugno composed hit songs for numerous artists, notably Miguel Bosé (the Festivalbar winning song “Super Superman”), Adriano Celentano (“Il tempo se ne va“, “Soli“), Luis Miguel (“Ragazzi di oggi“), Fausto Leali (“Io amo“), Peppino di Capri (“Il sognatore“), Ricchi e Poveri (“Canzone d’amore“), Fiordaliso (“Per noi” and “Se non avessi te“). Starting from 1987, when he co-hosted with Lino Banfi the Sunday television show Domenica in, Cutugno also had a successful career as a television presenter.

In 1990, at the refusal of Sanremo winners Pooh, Cutugno, who had placed second, was invited to represent Italy at the Eurovision Song Contest in Zagreb. He went on to win the contest with his own original composition “Insieme: 1992” (“Together: 1992“), a ballad which celebrated European political integration and the establishment of the European Union. Aged 46 years, 302 days, Cutugno became the oldest winner of the contest to date, surpassing the record set by André Claveau in 1958. Cutugno’s record stood until 2000, when the Olsen Brothers won the contest.  Along with Gigliola Cinquetti, Italy’s earlier Eurovision winner, he presented the 1991 contest, which was staged in Rome as a result of his victory.Italy would only win again with Måneskin in 2021.

In 2014, he was the main subject of a Facebook page, La stessa foto di Toto Cutugno ogni giorno (lit. “The same photo of Toto Cutugno every day”), which in a short time became an internet phenomenon, attracting thousands of likes, sharings and comments; the case eventually became the subject of a study of the Institute for Advanced Study in Pavia. In 2016, he returned to collaborate with Adriano Celentano, co-writing the song “Ti lascio amore” for the Mina–Celentano album Le migliori.