Caufield, who played right wing on a line centered by Hughes, scored a career-high six goals to reach 105 and pass forward Phil Kessel (104 goals from 2003-05), now with the Pittsburgh Penguins, for the NTDP lead.
"Going into the game you just want to win, so I don't think I was lucky, but the puck was bouncing my way, so I can credit my teammates and coaches for that," Caufield said. "It's just a really special night."
Caufield, who scored the six goals on 10 shots, is four goals from tying Auston Matthews, now with the Toronto Maple Leafs, for the most goals in an NTDP season. Matthews scored 55 with the U-18 team in 2014-15.
Hughes (5-foot-10, 168 pounds) has nine multipoint games during a 12-game point streak and 74 points (20 goals, 54 assists) in 36 games this season. He was No. 1 in NHL Central Scouting's midterm rankings of North American skaters eligible for the 2019 draft.
Kessel is third on the NTDP list (180 points), followed by Kane (172), a forward for the Chicago Blackhawks; Jeremy Bracco (168), a forward prospect for the Toronto Maple Leafs; and Matthews (167).
"With all the players who have come through the program and being able to pass some of those guys was really cool," Hughes said. "You look at the list with Keller, Auston Matthews and Patrick Kane; it's just cool to be mentioned with them."
Caufield (5-foot-7, 155) has 73 points (51 goals, 22 assists) in 50 games this season, and 153 NTDP points. He was No. 15 among North American skaters in the NHL Central Scouting midterm rankings.
The record-breaking goal and assist came at 16:54 of the third period.