Ronaldo sits second in the all-time list of leading international scorers behind Iran's Ali Daei, who scored 109 in his career. Daei, who played for Bayern Munich and Hertha Berlin at club level, featured for Iran from 1993 to his retirement in 2007.
The milestone goal came just before half-time following a foul just outside the Sweden penalty box. Ronaldo stepped up and fired an unstoppable shot into the top-left corner to beat a diving Robin Olsen. He later added another with an equally sublime strike in the second half, again beating Olsen with a superb shot from distance.
"I managed to beat this milestone of 100 goals and now [I'll go] for the record. It's step-by-step. I am not obsessed because I believe the records come in a natural way," Ronaldo said after the match.
The 35-year-old Juventus star has scored 49 of his 101 career goals with Portugal after turning 30, with his goals-per-game rate more than doubling.
The goals marked his seventh in seven matches all-time against Sweden, his most-punished opponent along with Lithuania, against which he has scored seven in just three matches.
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Ronaldo made his Portugal debut back in 2003 against Kazakhstan, coming on as a second-half substitute in a 1-0 victory.
He scored his first goal for Portugal in a 2-1 defeat against eventual champions Greece in the group stage of Euro 2004.
Ronaldo won his first international trophy with Portugal when they defeated France 1-0 in the final of Euro 2016, and also helped them to lift the inaugural UEFA Nations League title in 2019.
The former Real Madrid winger missed Portugal's first game of this season's Nations League due to a toe infection. Portugal won the game 4-1. Watching from the stands, Ronaldo was asked to wear a face mask by a stadium official.