Springer beat the reigning champion 6-3 to halt Anderson’s bid for a third successive title, overcoming two ton-plus checkouts by the Scot.
He will face Danny Noppert in the last 16, after the Dutchman edged past Oskar Lukasiak.
“(Danny) is a fantastic player. We played the last time in Budapest when I won the final,” said Springer.
“I know how good he is, and I know I have to play (at) the same level as today.”
Clayton delivered the performance of the day, averaging 106.78 in a 6-1 win over Valters Melderis, having opened with legs of 13, 11 and 11 darts.
Wessel Nijman also impressed, averaging more than 104 in a 6-2 victory over Ryan Searle.
"Playing Ryan Searle, I probably needed an average above 100, so I’m happy I did and happy with the way I played,” said Nijman.
"The goal (this year) was to get into the top 16, and the next goal was to win a Euro Tour. To do that before the summer, that’s my goal achieved for the whole year."
Nijman will play Liverpudlian Stephen Bunting, who beat Mickey Mansell 6-3.
Top seed Gian van Veen was defeated by Joe Cullen, who reached the last 16 of a European Tour event for the first time in 12 months.
James Wade ended a five-match losing run on the European Tour with a 6-3 win over Kim Huybrechts to set up a meeting with Nathan Aspinall, who beat Jeffrey de Zwaan 6-1.
Michael van Gerwen opened up his campaign with a 6-2 victory over Michael Unterbuchner.
Welsh star Gerwyn Price beat Dave Chisnall 6-4 to set up a meeting with Chris Dobey, who bettered Andrew Gilding 6-2.
Martin Schindler edged out Damon Heta 6-5 and will face Clayton, while Josh Rock and Ross Smith progressed with wins over Keane Barry and Cameron Menzies respectively.
Jermaine Wattimena beat Kevin Doets and will now take on Van Gerwen, while Krzysztof Ratajski also advanced and will face Cullen when the tournament concludes on Sunday.
Results
Round two
Afternoon session
Krzysztof Ratajski 6-4 Mike De Decker
Jermaine Wattimena 6-3 Kevin Doets
Wessel Nijman 6-2 Ryan Searle
Danny Noppert 6-5 Oskar Lukasiak
Chris Dobey 6-2 Andrew Gilding
Niko Springer 6-3 Gary Anderson
Stephen Bunting 6-3 Mickey Mansell
Josh Rock 6-3 Keane Barry
Evening session
Ross Smith 6-3 Cameron Menzies
Gerwyn Price 6-4 Dave Chisnall
Nathan Aspinall 6-1 Jeffrey de Zwaan
James Wade 6-3 Kim Huybrechts
Joe Cullen 6-3 Gian van Veen
Michael van Gerwen 6-2 Michael Unterbuchner
Martin Schindler 6-5 Damon Heta
Jonny Clayton 6-1 Valters Melderis