Finishing in 5min 33sec Matthews (Sunweb) was one second faster than Tom Bohli (BMC) over the 4km course set around Fribourg, Switzerland. Primoz Roglic (LottoNL-Jumbo) was third.
After a stellar 2017, when he won two Tour de France stages and the green jersey, Matthews had a low-key European spring season which included an injury after a crash.
"I had a rocky start to the season and things were difficult with my broken shoulder but I finally feel like things are on the up again," Matthews said.
"I didn't know how well I would feel after the weekend but I gave my best and I'm really pleased that I could finish it off with the win.
"It was a beautiful course and I had a lot of fun out there today. I really enjoy TT's, especially ones like these where I can use my power.
The six-day race continues with a 166km road stage from Fribourg to Delemont which includes a pair of Cat2 climbs.
"Tonight we'll just enjoy this win and tomorrow we'll focus on what we're going to do next," Matthews said.
Rohan Dennis, who is fine-tuning his form ahead of the Giro d'Italia claimed fourth in 5min 34:64sec while BMC team-mate and defending champion, Richie Porte finished inside the top twenty, 14 seconds behind Matthews in 18th place.