I te wā o te Pakanga Mexican-American (1846-1848), i ārahi a Twiggs i tētahi pirihimana i roto i te Ope Taua o te Whakahaere i ngā pakanga o Palo Alto
me te Resaca de la Palma. I whakatairangahia ia ki te rangatira rangatira i te tau 1846 ka whakahau i tetahi wehenga i te Pakanga o Monterrey. I uru ia ki te haerenga a Winfield Scott, e whakahau ana i tana wehenga tuarua o nga Regulars. I ārahi ia i te wehenga i ngā pakanga katoa mai i Veracruz ki Mexico City. I whara ia i te whakaekenga o Chapultepec. Whai muri i te hinganga o Mexico City, i tohua ia hei kawana hoia o Veracruz. I whakawhiwhia a Brigadier General Twiggs ki te hoari huihuinga e te Kaunihera i te Poutu-te-rangi 2, 1849. He mema taketake ia o te Karapu Aztec o 1847, he hapori hoia o nga rangatira i mahi i te Pakanga o Mexico.