After going down early, Penn State rallied back with four unanswered goals to secure the win.
Penn State men's basketball will play Illinois on February 21, while the women's team will play Ohio State on February 22.
The win over the Hawkeyes extended the Nittany Lions' nine-game winning streak and a perfect Big Ten record.
The Nittany Lions outshot Clarkson 81-48.
A 73rd minute go-ahead goal from captain Peter Mangione was the difference as the Nittany Lions gave Northwestern its first loss.
Sophia Gladieux scored two goals for her fourth multi-goal game of the season.