The influence of mechano-ultrasonic activation (MUA) and nano-additives (carbon nanotubes-CNT) on the interaction pathway of nickel–aluminum powder mixture at high heating rates was investigated. The optimum conditions of the mechano-ultrasonic activation, along with the phase and structure formation peculiarities of nickel–aluminum and nickel–aluminum–carbon nanotubes mixtures by thermal analysis method, the so-called high-speed temperature scanner (HSTS), were found out. The optimum duration of mechanical and ultrasonic activation aiming to achieve homogeneous distribution in the agitated mixtures was determined. A shift in characteristic temperatures of MUA mixtures by the influence of both heating rate and ultrasound on the Ni + Al interaction pathway for the mechano-activated (1, 3, 5 min) and 1 wt% CNT containing mixtures was observed. The formation patterns of NiAl + Ni₃Al mixture or pure NiAl phase was manifested according to the interaction mechanism (depending on solid–liquid or solid–solid state of intermediates). The effective activation energy values for the Ni + Al exothermic reactions of all studied systems were determined by the isoconversional method of Kissinger.