Midline lumbar interbody fusion (MIDLIF) and minimally invasive transforaminal interbody fusion (MIS-TLIF) are two minimally invasive lumbar fusion methods that have gained popularity in the past two decades. MIDLIF involves the use of cortical bone trajectory screws, whereas MIS-TLIF uses traditional pedicle screws. However, there is a significant lack of research directly examining the clinical efficacy of these two methods in treating single-segment lumbar degenerative diseases. Hence, the objective of our retrospective study is to assess and contrast the surgical and clinical results of MIDLIF and MIS-TLIF. The study population comprised 133 patients diagnosed with single-segment lumbar degenerative disease that received treatment using either MIDLIF (n = 65) or MIS-TLIF (n = 68) in our department from January 2017 to January 2019. The fusion rates for MIDLIF were consistently lower than MID-TLIF at all post-operative time periods of follow-up, however, the differences between the two groups were not statistically significant. The 1-year fusion rates were 81.5% (MIDLIF) and 83.8% (MIS-TLIF) (P = 0.728), and the 2-year fusion rates were 87.7% (MIDLIF) and 91.2% (MIS-TLIF) (P = 0.513). The final follow-up fusion rates were 93.8% (MIDLIF) and 95.6% (MIS-TLIF) (P = 0.653). MIDLIF had several advantages over MIS-TLIF, including a shorter operative time (135.2 ± 15.70 vs. 160.1 ± 17.2 min, P < 0.001), decreased intraoperative blood loss (147.9 ± 36.4 vs. 169.5 ± 24.7 mL, P < 0.001), and a shorter length of hospital stay (10.8 ± 3.1 vs. 12.4 ± 4.1d; P = 0.014). No significant differences were seen between the groups in terms of the postoperative day of ambulation, Oswestry dysfunction index (ODI) scores, and visual analog scale (VAS) scores for leg and lower back pain (P > 0.05). Although not significant (P = 0.707), MIDLIF (13.8%) had fewer overall complications than MIS-TLIF (16.2%). Therefore, compared to MIS-TLIF, MIDLIF provides perioperative benefits while achieving the same outcomes as MIS-TLIF in terms of fusion rate, pain relief, functional improvement, and complication rate.