The objective of this study was to investigate the effects of intensive fattening with total mixed rations (TMR) on carcass characteristics, meat quality, and chemical composition of the yak meat. Theoretical data has been provided for evaluating the quality of yak meat during natural grazing and short-term fattening. Based on the analysis, we found that in fattening yak, the carcass weight (CWT) was increased by 106.43%, whereas the cooking loss, tenderness, and drop loss were significantly improved due to higher intramuscular fat content and lower moisture (P < 0.05). Protein, fat, calcium, and amino acids were also much higher (P < 0.01) in fattening yak compared with the grazing yak. The levels of albumin (ALB), lactate dehydrogenase (LDH), triglyceride (TRIG), and amylase (AMYL) in serum indicated better nutritional status for fattening yaks. The transcriptomics analysis showed that the high expression of ACSL1 and ACACB genes improved the synthesis and deposition of fat in fattening yak, whereas the regulation of SLC7A8, ATP1A4, ATP1A1, SLC3A2, and CPA3 gene expression weakened the proteolysis. These results indicated that fattening with TMR improves the yield and quality of the yak meat.