The decade began with the advent of new manufacturers like Bultaco, CZ, Benelli and, above all, Honda, challenging the dominion of Cascina Costa's bikes. The new competitors didn't look like a threat to Carlo Ubbiali and John  Surtees. Ubbiali won the World Championships in the 125 and 250 classes, while Surtees completed MV's four-of-a-kind with victories in the 350 and 500 categories. At the end of the season "Big John" left bike racing for F1, where he joined "The Drake" Enzo Ferrari's team to win a Formula 1 World Championship  as well (in 1964).  The new well-to-do society documented in Fellini's masterpiece "La dolce vita" did not seem to have much to do with the motorcycle market, which was suffering from a drop in demand that forced even MV Agusta to retire from racing temporarily. Ubbiali and Surtees's winning bikes continued to be successful, however, thanks to the commitment of a select few privateers who were able to gain Count Domenico Agusta's confidence.

These included Gary Hocking, who easily won the 350 and 500 categories with the MV Agusta Privat, a curious name applied to the fuel tank to indicate that he did not officially represent the manufacturer. The next year saw the arrival at Cascina Costa of Mike Hailwood, a rider that thrilled the crowds with his innate class. Nicknamed Mike "the Bike" in the press, Hailwood dominated the five hundred class completely from 1962 to 1965 before giving way to the rising Giacomo Agostini.

The Privat tag disappeared halfway through the '60s and MV Agusta began to race officially again, with confidence boosted by an extraordinary plan. A 3 cylinder 4 stroke machine inclined by 10°, initially a 350cc and then developed into a 500cc, was produced with double cam distribution with four valves per cylinder and seven speed gearbox. As for the bike, the frame was…formed out of a double cradle of steel tubes with a square fork permitting inclination of the rear shocks. MV Agusta's new weapon, which Count Domenico insisted on entering in the very first official race, immediately revealed its potential with the help of the talented young Giacomo Agostini. "Ago" claimed a resounding victory on the Nurburgring track at the expense of team-mate Hailwood, who came in second on his four cylinder bike.

In 1966  Hailwood  went on to Honda and Agostini became MV Agusta's top rider. The two ex team-mates faced off in the premiere class, and Ago did not win until Spa Francorchamps. After his victory on the Belgian track Agostini went on to a three-cylinder bike (a 474cc oversized 350) and beat Hailwood at Monza in the first of the thirteen races he was to win for MV Agusta. The following year Hailwood had a brand new 6 cylinder 350 and a 4 cylinder 500 at his disposal, but despite "Mike the Bike's" heavy artillery both Championships were won by the Italian, who sealed the 500 category in the last race. In 1968, when Honda retired from racing, Hailwood had to race the season as a private rider, and couldn't compete with Agostani, who won in the 350 and 500 categories. The script that closed the decade was to be repeated throughout the first half of the ‘70s.