The back-rower required three periods of medical attention from Wales physiotherapist Mark Davies before finally conceding defeat and walked down the tunnel in the 19th minute, casting doubt over a possible call-up in the short-term to South Africa.
Wales caretaker coach Robin McBryde said: "Ryan had a bump early on and struggled to get over it. We tried to give him time and let him clear his head but he wasn't able to do so.
"He will be disappointed because he has led the side really well both on and off the pitch. Ryan had his own goals set for this tour and it's unfortunate that his tour was cut short.
"We don't know how bad it is and it's too early to say. We will wait to see what the physiotherapists say.
"But the players on stand-by played well and we're in constant touch with the coaches out in South Africa so if they need to find out about a player then we'll be in touch."
The 2008 Grand Slam winning captain will have been disappointed not to stake his claim further for a late call-up to face the Springboks and cement the Wales captaincy for the autumn series.
"Of course I would want to continue as Wales captain. It's a huge honour and it is something I have really enjoyed," said Jones.
"It came as a shock 18 months ago and it has been difficult at times but it's something that I don't think I would relinquish lightly. Being the first person out of the tunnel at the Millennium Stadium is the best position to be in.
"This season has been a mixed bag and has gone well for me in patches and not so well in others. But you have to move on and make sure you learn from your mistakes."
Wales brushed aside the Eagles with ease in their 600th Test match in a six-try romp including a fine double for young Scarlets centre Jonathan Davies.
Mark Jones opened the try-scoring before Davies, winning just his second cap, and a penalty try allowed the tourists to cruise into a 27-3 half-time lead.
The hosts rallied briefly early in the second half when centre Alipate Tuilevuka crossed but they needed a fight-back as imposing as the Sears Tower to inflict their first win over the Three Feathers in seven meetings.
But Tom James, Gareth Cooper and Davies touched down either side of JJ Gagiani's consolation for the USA to end the season on a high.
USA: C Wyles; G DeBartalo, A Tuilevuka, R Suniula, K Swiryn (J Sifa, 65); A Malifa (M Hercus, H-T), M Petri (capt, T Usasz, 69); M Moeakiola (M MacDonald, 54), C Biller (B McClanahan, 66), W Johnson (JJ Gagiani, 76), J Van Der Giessen, H Smith, L Stanfill, N Johnson, P Dahl
Tries - A Tuilevuka, JJ Gagiani. Con - G DeBartalo. Pen - G DeBartalo
Wales: D Evans (J Spratt, 54); T James (G Cooper, 70), J Davies, A Bishop, M Jones; N Robinson (D Biggar, 64), D Peel; Duncan Jones (J Yapp, 64), G Williams, J Yapp (C Mitchell, 48), I Gough (L Charteris, 48), Deiniol Jones, Dafydd Jones, R Jones (capt, S Warburton, 19), R Sowden-Taylor (R Hibbard, 26).
Tries - M Jones, J Davies (2), Penalty try, T James, G Cooper. Cons - N Robinson (4), D Biggar (2). Pens - N Robinson (2)
Referee: Matt Goddard (Australia)